Opposing activity changes in AMP deaminase and AMP-activated protein kinase in the hibernating ground squirrel.
Hibernating animals develop fatty liver when active in summertime and undergo a switch to a fat oxidation state in the winter. We hypothesized that this switch might be determined by AMP and the dominance of opposing effects: metabolism through AMP deaminase (AMPD2) (summer) and activation of AMP-ac...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4391924?pdf=render |
| _version_ | 1819171735461691392 |
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| author | Miguel A Lanaspa L Elaine Epperson Nanxing Li Christina Cicerchi Gabriela E Garcia Carlos A Roncal-Jimenez Jessica Trostel Swati Jain Colin T Mant Christopher J Rivard Takuji Ishimoto Michiko Shimada Laura Gabriela Sanchez-Lozada Takahiko Nakagawa Alkesh Jani Peter Stenvinkel Sandra L Martin Richard J Johnson |
| author_facet | Miguel A Lanaspa L Elaine Epperson Nanxing Li Christina Cicerchi Gabriela E Garcia Carlos A Roncal-Jimenez Jessica Trostel Swati Jain Colin T Mant Christopher J Rivard Takuji Ishimoto Michiko Shimada Laura Gabriela Sanchez-Lozada Takahiko Nakagawa Alkesh Jani Peter Stenvinkel Sandra L Martin Richard J Johnson |
| author_sort | Miguel A Lanaspa |
| collection | DOAJ |
| description | Hibernating animals develop fatty liver when active in summertime and undergo a switch to a fat oxidation state in the winter. We hypothesized that this switch might be determined by AMP and the dominance of opposing effects: metabolism through AMP deaminase (AMPD2) (summer) and activation of AMP-activated protein kinase (AMPK) (winter). Liver samples were obtained from 13-lined ground squirrels at different times during the year, including summer and multiples stages of winter hibernation, and fat synthesis and β-fatty acid oxidation were evaluated. Changes in fat metabolism were correlated with changes in AMPD2 activity and intrahepatic uric acid (downstream product of AMPD2), as well as changes in AMPK and intrahepatic β-hydroxybutyrate (a marker of fat oxidation). Hepatic fat accumulation occurred during the summer with relatively increased enzymes associated with fat synthesis (FAS, ACL and ACC) and decreased enoyl CoA hydratase (ECH1) and carnitine palmitoyltransferase 1A (CPT1A), rate limiting enzymes of fat oxidation. In summer, AMPD2 activity and intrahepatic uric acid levels were high and hepatic AMPK activity was low. In contrast, the active phosphorylated form of AMPK and β-hydroxybutyrate both increased during winter hibernation. Therefore, changes in AMPD2 and AMPK activity were paralleled with changes in fat synthesis and fat oxidation rates during the summer-winter cycle. These data illuminate the opposing forces of metabolism of AMP by AMPD2 and its availability to activate AMPK as a switch that governs fat metabolism in the liver of hibernating ground squirrel. |
| first_indexed | 2024-12-22T19:56:01Z |
| format | Article |
| id | doaj.art-222b83b5765c4b3580717d460afe9be5 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T19:56:01Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-222b83b5765c4b3580717d460afe9be52022-12-21T18:14:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01104e012350910.1371/journal.pone.0123509Opposing activity changes in AMP deaminase and AMP-activated protein kinase in the hibernating ground squirrel.Miguel A LanaspaL Elaine EppersonNanxing LiChristina CicerchiGabriela E GarciaCarlos A Roncal-JimenezJessica TrostelSwati JainColin T MantChristopher J RivardTakuji IshimotoMichiko ShimadaLaura Gabriela Sanchez-LozadaTakahiko NakagawaAlkesh JaniPeter StenvinkelSandra L MartinRichard J JohnsonHibernating animals develop fatty liver when active in summertime and undergo a switch to a fat oxidation state in the winter. We hypothesized that this switch might be determined by AMP and the dominance of opposing effects: metabolism through AMP deaminase (AMPD2) (summer) and activation of AMP-activated protein kinase (AMPK) (winter). Liver samples were obtained from 13-lined ground squirrels at different times during the year, including summer and multiples stages of winter hibernation, and fat synthesis and β-fatty acid oxidation were evaluated. Changes in fat metabolism were correlated with changes in AMPD2 activity and intrahepatic uric acid (downstream product of AMPD2), as well as changes in AMPK and intrahepatic β-hydroxybutyrate (a marker of fat oxidation). Hepatic fat accumulation occurred during the summer with relatively increased enzymes associated with fat synthesis (FAS, ACL and ACC) and decreased enoyl CoA hydratase (ECH1) and carnitine palmitoyltransferase 1A (CPT1A), rate limiting enzymes of fat oxidation. In summer, AMPD2 activity and intrahepatic uric acid levels were high and hepatic AMPK activity was low. In contrast, the active phosphorylated form of AMPK and β-hydroxybutyrate both increased during winter hibernation. Therefore, changes in AMPD2 and AMPK activity were paralleled with changes in fat synthesis and fat oxidation rates during the summer-winter cycle. These data illuminate the opposing forces of metabolism of AMP by AMPD2 and its availability to activate AMPK as a switch that governs fat metabolism in the liver of hibernating ground squirrel.http://europepmc.org/articles/PMC4391924?pdf=render |
| spellingShingle | Miguel A Lanaspa L Elaine Epperson Nanxing Li Christina Cicerchi Gabriela E Garcia Carlos A Roncal-Jimenez Jessica Trostel Swati Jain Colin T Mant Christopher J Rivard Takuji Ishimoto Michiko Shimada Laura Gabriela Sanchez-Lozada Takahiko Nakagawa Alkesh Jani Peter Stenvinkel Sandra L Martin Richard J Johnson Opposing activity changes in AMP deaminase and AMP-activated protein kinase in the hibernating ground squirrel. PLoS ONE |
| title | Opposing activity changes in AMP deaminase and AMP-activated protein kinase in the hibernating ground squirrel. |
| title_full | Opposing activity changes in AMP deaminase and AMP-activated protein kinase in the hibernating ground squirrel. |
| title_fullStr | Opposing activity changes in AMP deaminase and AMP-activated protein kinase in the hibernating ground squirrel. |
| title_full_unstemmed | Opposing activity changes in AMP deaminase and AMP-activated protein kinase in the hibernating ground squirrel. |
| title_short | Opposing activity changes in AMP deaminase and AMP-activated protein kinase in the hibernating ground squirrel. |
| title_sort | opposing activity changes in amp deaminase and amp activated protein kinase in the hibernating ground squirrel |
| url | http://europepmc.org/articles/PMC4391924?pdf=render |
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